THE EFFECTS OF ALPHA-ACTININ-3 KNOCKOUT ON BONE LENGTH AND DENSITY IN THE CRANIAL BASE AND CALVARIAL BONES

Abstract

The R577X ACTN3 stop codon polymorphism associates with skeletal Class II and open bite malocclusions. In mice Actn3 KO condylar growth is altered, producing an increase in trabecular number, but decrease in trabecular thickness and separation. This study expands these findings by comparing bone length and quality in the cranial base and calvarial bones of Actn3-/- and Actn3+/+ genotype mice. The heads of 20, 3-month old female mice (10 WT and 10 KO) were scanned using the Skyscan 1172 microCT scanner at a resolution of 9.4µm using a 0.5mm Aluminum filter. The raw microCT data was reconstructed. The macro-anatomy (linear measurements) were obtained using the line measurement tool in CTAn software. Micro-anatomy (Bone volume and trabeculation) were also assessed using the CTAn software. The presphenoido-basisphenoidal and basisphenoido-basioccipital synchondroses were evaluated in entirety and five sutures (frontal, parietal, fronto-parietal, bregma and pari) were segmented as a 1mm wide X 1mm deep X height of suture region of interest. No statistically significant difference between Actn3 KO and WT mice was found in linear measurements of the cranial base and calvarial bones. The ratio of bone volume to total volume (BV/TV) and trabecular separation (Tb. Sp.) of Actn3 KO and WT suture sites were found to have no statistically significant difference (p range 0.9957-0.0953) The Tb. Sp. of the presphenoido-basisphenoidal synchondrosis was the only location to show statistical significance (p = 0.0331). Tb.Sp of the basisphenoido-basioccipital synchondrosis was found to be nearly statistically significant (p= 0.1818), with power analysis predicting significance at n=51. As seen in previous studies, Actn3 KO mice are shown to have an altered bone quality in cartilaginous growth areas, including the mandibular condyle and cranial base synchondroses.